How genotype allows protection against a terrible disease

In certain regions of Africa where malaria in on a rampage, you’ll find that a significant number of the population has sickle cell anemia. In America, populations have selected against such a disease because its effects can be debilitating and sometimes lead to death. But in Africa those who have a mild case of sickle cell anemia actually have a lower risk of contracting malaria. Individuals with sickle cell anemia have crescent shaped red blood cells which interfere with the protein hemoglobin’s ability to pick up oxygen. Scientists have found that something about this conformation provides protection against malaria for the host. The exact mechanism has yet to be fully elucidated by scientists, but it is of great interest to them and some think it has to do with a special immune response from the body. Others think that the protective mechanism is due to a tolerance to the effects of the disease.

Nonetheless, they have found that individuals who are heterozygous for sickle cell anemia are more likely to survive in regions that have malaria and therefore have an advantage over those who are homozygous. This phenomenon is referred to as overdominance or heterozygous advantage.

In the case of heterozygous advantage where codominace is present, both the good and bad alleles are expressed. With sickle cell anemia this has proved to be a protective mechanism against malaria. That’s why the bad alleles haven’t been selected out of the populations in regions where malaria is more prevalent.

Codominance means that both alleles, which most people call genes, are expressed in the individual. Codominance differs from complete dominance because there are three different phenotypes rather than just two. For an individual that is homozygous for both of the good alleles, he or she will not be afflicted by the disease. For an individual that is homozygous for the bad alleles, he or she will be afflicted by the disease and therefore be less fit for survival.

In nature, this happens without human intervention. In order to maintain a population that is fit to survive, nature will select favorable genes to be continued in a population. Often times an unfit gene means that the survival rate is decreased causing the bad genes to be selected against. If people or animals with the bad genes die before they are able to reproduce, then the bad genes will become less prominent in the population. In this case, individuals who would normally be weeded out are actually selected for because of the special circumstance of malaria resistance.

For those who are more scientifically inclined I have provided some further insight for a potential molecular mechanism for the protection against malaria.

In the study I have linked above, mouse models were used to demonstrate a molecular mechanism for protection against sickle cell anemia. The study was not conducted in humans due to the ethical ramifications of such a study. It was found that protection occurs not as an avoidance of parasites sequestering the host but as a tolerance to the effects of sickle cell anemia. Tolerance to the disease is carried out by several different contributing factors.

-Mutations on the beta-strand of human Hb contribute to tolerance by decreasing the severity of the disease. This done by stopping tissue damage before it occurs.

-Higher expression of HO-1 (form the gene Hmox1) is associated with individuals having the HbS mutation. This is triggered by a higher number of free heme, which induces this gene to be expressed.

-Production of CO by means of HO-1 catabolism suppresses cytotoxic levels of free heme and prevents the progression of the disease.

It ought to be noted that CO does not play a role in host parasite load, meaning that it does not eliminate the parasite from the host. This particular article put a lot of emphasis on and deemed tolerance responsible for the protective mechanism against malaria in mouse models.

Science is cool, my friends! Also this topic was suggested by myinkdropsblog , thank you for putting this idea in the hat!